ABSTRACT The overarching goal of this project is to develop, validate and implement a new modality for noninvasive functional imaging of neural currents deep in the human brain through the skull at unprecedented spatial and temporal resolution. Transcranial Acoustoelectric Brain Imaging (tABI) is a disruptive technology that exploits an ultrasound (US) beam to transiently interact with physiologic current, producing a radiofrequency signature detected by one or more surface electrodes. By rapidly sweeping the US beam and simultaneously detecting the AE modulations, 4D current density images are generated. This approach overcomes limitations with electroencephalography (EEG), which suffers from poor spatial resolution and inaccuracies due to blurring of electrical signals as they pass through the brain and skull, and, unlike fMRI and PET that measure slow ?intrinsic? signals, tABI directly maps fast time-varying current within a defined brain volume at the mm and ms scales. As a disruptive modality for noninvasive human brain imaging, tABI offers the following benefits: 1) High spatial resolution determined by the US focus (0.5 ? 3 mm); 2) Real-time, volumetric imaging of local field potentials and evoked activity; 3) 4D imaging of neural currents from deep brain structures without assuming the conductivity distribution; and 4) Co-registration of neural currents (tABI) with brain structure and motion (pulse echo US) and cerebral blood flow (Doppler). Our multidisciplinary team of engineers, neuroscientists, psychologists, and imagers will overcome the grand challenge of detecting the weak AE interaction signal through the human skull and demonstrate a safe, revolutionary modality for electrical brain imaging at the mm and ms scales in healthy volunteers. 1) Develop next-generation integrated platform for tABI of the human brain through skull; 2) Optimize, calibrate, and validate tABI using human head and in vivo swine models; 3) Assess extraoperative tABI for mapping patients with intractable epilepsy referred for surgery; and 4) Assess performance of tABI for mapping somatotopic organization in healthy volunteers. If successful, this project will deliver a safe, revolutionary and mobile modality for noninvasive human brain imaging that would transform our understanding of brain function and help diagnose, stage, monitor and treat a wide variety of neurologic (e.g., epilepsy, Parkinson's), psychiatric (e.g., depression) and behavioral (e.g., OCD) disorders.